Clinical and pathological significance of serum anti-PD-1 autoantibodies in acute-onset and chronic autoimmune hepatitis

Abstract Background Acute-onset autoimmune hepatitis (A-AIH) poses diagnostic challenges because autoantibodies are frequently absent or serum IgG levels may only be mildly elevated. Autoantibodies against the immune checkpoint molecule PD-1 have been detected in patients with chronic AIH (C-AIH). To clarify the clinical and pathological significance of anti-PD-1 autoantibodies, we examined their association with the clinical features of patients with liver diseases, including A-AIH, C-AIH, primary biliary cholangitis (PBC), and drug-induced liver injury (DILI). Methods We compared the clinical characteristics and serum anti-PD-1 autoantibody titers of patients with A-AIH, C-AIH, PBC, and DILI ( n = 72, 45, 41, and 19, respectively). Correlations between autoantibody titers and biochemical parameters were assessed to identify the factors that discriminate between the diseases. To reduce non-specific IgG response, anti-PD-1 autoantibody titers were normalized to the serum IgG levels. The liver histology was evaluated in a subset of patients with AIH. Results A-AIH caused severe liver parenchymal and portal inflammation. The anti-PD-1/IgG ratio showed positive correlations with AST and ALT, but only weak correlations with ALP and γ-GTP. Anti–PD-1/IgG ratio was the highest in A-AIH, followed by DILI, C-AIH and PBC. Histological findings showed that anti–PD-1/IgG ratio was associated with severe inflammation, but not with centrilobular necrosis. Conclusions The serum anti-PD-1 autoantibody/IgG ratio was significantly elevated in A-AIH compared with that in C-AIH and PBC, and A-AIH was independently distinguished from C-AIH. These markers may assist with the assessment of acute-onset liver inflammation and clinical phenotyping of AIH.